Significance: There is growing concern about accelerated aging phenotypes and degenerative outcomes among the rapidly increasing cancer survivor population in the United States. Neurocognitive disorders and physiologic frailty are two highly debilitating complications of cancer survivorship that can persist several years after cancer treatment, compromising quality of life in survivors. Given that adult cancer is a disease of aging, that the older adult US population is expanding, and more than two-thirds of cancer survivors are >65 years old, cancer survivors will constitute an increasing proportion of the rapidly aging population. If survivors experience earlier and greater cognitive decline, incident dementia and frailty than their counterparts who have no history of cancer, the cost of caring for the elderly in the US will increase tremendously, with enormous implications for healthcare service delivery. Evidence supports that aberrant inflammation resulting in altered circulating inflammatory protein profiles is one pathophysiologic mechanism underlying neurocognitive disorders and many adverse health conditions in cancer survivors. But current studies examining the role of inflammation in these outcomes are either limited to breast cancer, cross-sectional, based on clinic cohorts, include few inflammatory proteins or have short duration of follow-up. These limitations can be overcome by prospective population-based studies of survivors of different cancers, that assay a large array of inflammatory proteins at multiple visits over time.
Specific Aims :
We aim to use data from 633 ?5 year survivors of prostate, breast, colorectal, endometrial and bladder cancers and 5323 cancer-free individuals who attended visit 5 in 2011-2013, in the Atherosclerosis Risk in Communities (ARIC) study to: 1) Determine if higher levels of systemic inflammation are associated with neurocognitive outcomes (cognitive decline and incident dementia) in survivors (>65 years of age) in the U.S.; 2) Determine if higher levels of systemic inflammation are associated with physiologic frailty in the cancer survivors (>65 years of age) in the U.S.; and 3) Determine if higher levels systemic inflammation are associated with mortality from causes other than their cancer in the cancer survivors (>65 years of age) in the U.S. Approach:
Aim 1 will develop a proteomics inflammatory measure and use linear regression models and Cox proportional hazard models to evaluate the association of higher systemic inflammation with the risk of cognitive decline and incident dementia respectively in cancer survivors.
Aim 2 will use multinomial regression to evaluate the association of higher systemic inflammation with physiologic frailty in cancer survivors.
Aim 3 will use Cox hazard models to examine the association of higher systemic inflammation with mortality from non-cancer causes among cancer survivors. Fellowship Information: Through a combination of coursework, professional skills development, and mentored research training, the proposed training program will equip Ms. Ugoji with the knowledge, skills, and experience to complete the aims of the proposed research and become a successful epidemiologist, studying aging and long-term outcomes in cancer survivors.
There is growing concern about accelerated aging phenotypes and degenerative outcomes among the rapidly increasing cancer survivor population in the United States. This study will determine if higher levels of systemic inflammation are associated with future risk of neurocognitive outcomes (cognitive decline and incident dementia), physiologic frailty and mortality from non-cancer causes in cancer survivors. Findings from this study will contribute seminal knowledge about the prospective contribution of systemic inflammation to neurocognitive outcomes, physiologic frailty and mortality in cancer survivors, and inform preventive, surveillance and clinical management strategies to reduce these complications, improve health and prolong lives of cancer survivors.
